Licit and illicit drug use places a large burden on the nation's health care systems and the economy, costing more than $500 billion annually. Addiction is a chronic brain disease that leads to a compulsive desire for drugs despite significantly harmful consequences, including direct effects on health as well as detriments to society, including disintegration of families, child abuse, loss of employment, and a broad array of crimes. Reprogramming of human somatic cells to alter cellular identity has enormous potential for neurological disease modeling, high-throughput drug screening, cell therapy, and personalized medicine. However, several challenges remain before patient-specific cells produced by reprogramming can provide reliable insights into neurological disease mechanisms (e.g., Drug abuse/ addiction, other neurological disorders) or be efficiently applied to drug discovery and transplantation therapy. Using our innovative patented technology to develop Artificial 3D Microenvironment Niche and screen for reprogramming small molecules (US Patent # 9045737), we have developed a preliminary small molecule cocktail that efficiently (up to 50% of starting cell numbers, mostly Glutamatergic Neurons) and directly converts human fibroblasts into neurons, bypassing the neural progenitor stage (Chemically induced Neurons, hCiN). In this Phase I proposal, we attempt to demonstrate the feasibility of this methodology by optimizing our preliminary hCiN cocktails while investigating hCiN functionally with molecular, cellular, electrophysiological assays and in a mouse brain transplantation model.